Microarrays for high-throughput analysis of biological compounds are known in the biotechnology field. Microarrays generally consist of a substrate, such as a slide or chip made of glass, plastic or silicon, upon which is attached an array of biological probes representing discrete binding or reaction sites for target biological compounds. Various types of probes are known, including nucleic acids, proteins, ligands, antibodies or other cellular proteins. For example, a typical DNA microarray includes an array, or matrix, of DNA probes representing discrete binding sites for at least some of the genes or gene products (e.g., cDNAs, mRNAs, cRNAs, polypeptides, and fragments thereof) in an organism's genome.
Microarrays have various applications, depending upon the probes used and the target compounds to be analyzed. For example, DNA microarrays have been used to study gene expression profiles, such as analyzing the transcriptional state of a cell exposed to graded levels of a drug of interest. Protein microarrays, including proteome microarrays representing most or at least some encoded proteins for a particular organism, may be used to study a wide variety of biochemical activities, such as protein-protein interactions, protein-lipid interactions, identifying the substrates of protein kinases, or identifying the protein targets of small molecules (MacBeath and Schreiber, 2000, Science 289:1760-1763; Zhu et al., 2001, Science 293:2101-2105). Similarly, a microarray having an ordered array or matrix of antibodies may be used for high-throughput screening of antibody-antigen interactions (de Wildt et al., 2000, Nature Biotechnology 18:989-994).
While microarrays are generally known and used in a wide variety of applications, available apparatus and systems for storing and processing microarrays have several shortcomings. For example, microarrays are typically placed in conventional microscope slide boxes or similar containers, which may not provide adequate protection during shipping and storage. Moreover, there is a potential to damage the microarray substrate or disrupt the array of biological probes when placing microarrays into, or removing them from, such a container.
During high-throughput processing of biological samples using microarrays, a common bottleneck is the selective binding or other reaction step between biological probes on a microarray and target compounds in the biological sample of interest. In the case of nucleic acid microarrays, for example, the selective binding step is often called the “hybridization” step, and is the process by which cDNA, cRNA or other nucleic acids in a sample bind selectively (i.e., hybridize) to complementary nucleic acid probe sequences (e.g., DNA or RNA) on the substrate. Preferable experimental protocols are best implemented if microarrays can be processed in pairs (sample vs. control or reference) or groups. Prior to the present invention, however, no suitable microarray processing apparatus or methods were available to handle microarray hybridization or other reactions in pairs or groups (analogous to 96-well plates, microcentrifuge tubes, or multi-well strips) for high-throughput sample processing.
In addition to their inability to process groups of samples, previously disclosed microarray processing systems have several other disadvantages. For example, many of the available hybridization devices utilize mechanical sealing mechanisms and fasteners, such as removable screws, clips, latches, screw caps and gaskets. Such devices are not desirable or practical for high-throughput processing of microarrays as they are generally closed systems, relatively complicated to use, expensive to manufacture, and/or they are not configurable with standard format footprints. Alternatively, systems employing plastic bags are relatively simple and inexpensive, however they do not provide sufficient rigidity for use with liquid dispensing robots. Other relatively simple systems utilize coverslip-type hybridization chambers placed on a microarray slide, however such systems have insufficient hybridization solution volumes and do not provide protection for microarray slides during processing or storage. Thus, there exists a need for efficient, cost-effective apparatus and methods for shipping, storing, and high-throughput processing of all types of microarrays.
Discussion or citation of a reference herein shall not be construed as an admission that such reference is prior art to the present invention.